New generation of antibiotics

How scientists are fighting antibiotic resistance

Since antibiotics were first developed at the start of the twentieth century, they have saved millions of lives (penicillin alone is estimated to have saved 200 million lives and counting), rendering a large number of deadly infections mere annoyances as people work their way through the prescribed dosages.

Or don’t. There are many reasons cited for the rise in antibiotic resistance, the most common being their misuse (i.e. not finishing a dose, taking it preventively, attempting to treat viral instead of bacterial illnesses, etc.). And then there’s lack of investment from big drug companies (there’s less money in meds that must be taken for 10 days instead of months or years), careless disposal (i.e. dumping in rivers), and giving to livestock (to fatten animals, not just treat illnesses). Many experts agree that these have all worked together to create the perfect storm for antibiotic resistance.

Governments and agencies alike, including the World Health Organization, call it one of the largest health crises of our time. As antibiotics become less effective, people are once again dying from simple infections. In Europe alone, 25,000 people die every year from antibiotic-resistant bacteria contracted in hospitals, while the CDC estimates that antibiotic-resistant bacteria cause two million illnesses and 23,000 deaths a year in the U.S. In the not-too-distant future, people going in for basic surgeries may have to weigh the risk of contracting an infection for which there is no cure. Some estimates put the annual death toll at 10 million.

“Some people are not going to be able to have elective hip and knee replacements because they’ll be at such high risk of infections,” infectious disease specialist Dr. Judy Stone told me. “It’s going to preclude a lot of elective surgery. And people are going to die from their infections, just as people used to all the time.”

“This is one case where governments need to act,” Nobel Prize–winning chemist Venki Ramakrishnan recently told Scientific American. “Antibiotics by their nature are not going to be the same class of money-maker. So I think that governments really need to get involved in the development of new antibiotics. They have to think of this as something generally good for society, the same reason that governments fund education, roads, police, defense and so on.”

In its review of 114 countries, WHO recommends that in order to tackle resistance, policymakers and industry need to develop new tools to fight a problem that already affects every pocket of the globe.” In other words, it’s time for new and better antibiotics, or new approaches to killing bacteria without killing the host. So who is doing what to unleash a new generation of antibiotics?

President Obama’s 2016 budget made a big splash last month when it called for doubling its investment in the fight against antibiotic resistance, devoting $1.2 billion to “improve antibiotic stewardship; strengthen antibiotic resistance risk assessment, surveillance, and reporting capabilities; and drive research innovation in the human health and agricultural sectors.”

Some spending is already bearing fruit as researchers travel the world in search of answers in the unlikeliest of places, including the guts of insects and the mud and sediment from deep sea trenches.

It’s an old trick, really – aspirin is essentially plant extract, and penicillin comes from fungus. In fact, some estimate that more than half of all medicines used today are either derived from or inspired by bacteria, plants, or animals; it’s a matter of looking in the right places. “Essentially, we’re looking for isolated populations of organisms,” one researcher told Reuters. “They will have evolved differently and therefore hopefully produce new chemistry.”

One citizen science project, Drugs from Dirt, aims to sequence the genomes of bacteria and other organisms in soils around the world. Along those lines, and perhaps most promising of all, an actual new class of antibiotics was discovered in January – for the first time in 30 years – and the method of discovery is novel, too. Not only has the drug cured severe infections (in test tubes and mice, at least), it is doing so without any identifiable side effects.

The method is “unusual,” as the New York Times put it, because scientists were able to extract the new drug, called teixobactin, from bacteria that live in dirt and then — and this is key — get it to grow in the lab: “The method developed to produce the drug has the potential to unlock a trove of natural compounds to fight infections and cancer — molecules that were previously beyond scientists’ reach because the microbes that produce them could not be grown in the laboratory.”

The inspiration behind the novel approach is that absolutely everything on the planet is teeming with microbes, which are engaged in a constant epic battle of survival of the fittest. Mid-fight, the microbes secrete biological weapons, aka antibiotics. Extracting those from the natural environment (teixobactin comes from a “grassy field in Maine,” the researchers say) by diluting a soil sample that is placed on special equipment allowed scientists to continue to grow them by immersing that equipment into a box of the very soil from which the diluted sample was extracted. From there, samples can divide and colonize, but these are “domesticated” colonies able to be grown in petri dishes.

“Essentially, we’re tricking the bacteria,” said Dr. Kim Lewis, the senior author of the article and director of the Antimicrobial Discovery Center at Northeastern University in Boston. And that’s not easy. Tricking, outsmarting, evolving faster — however it’s put, humans have had a tough time throughout history being one step ahead of bacteria.

Teixobactin has turned out to be the most promising drug isolated from 10,000 strains of bacteria the researchers were able to screen. In test tubes at least, it killed staph, strep, anthrax, and tuberculosis, and because it’s able to kill bacteria by blocking the fatty molecules that help construct cell walls, those molecules are less likely to change and develop resistance. While the team identified 25 other candidates, most came with serious baggage, like toxicity or insolubility. The team is, however, testing one further because in spite of its toxicity, it has the potential to help fight cancer.

Of course, whether the drug works so well in humans remains to be seen, with clinical trials at least two years out and thus drug development at least five or six. Dr. William Schaffner, an infectious disease specialist at Vanderbilt University, cautioned that toxicity could be a problem when moving to humans, but he also told the Times that the research is “ingenious” and admitted, “We’re in desperate need of some good antibiotic news.”

Not everyone is optimistic about the latest developments. Some question whether it’s wise to think of a magic bullet existing at all, the idea being that “resistance is inevitable,” as Michael Fischbach, a bioengineering and therapeutic sciences professor at the University of California, San Francisco, told the Wall Street Journal recently. “There’s always a need to innovate.”

In other words, bacteria may always be able to outsmart our greatest technological and chemical achievements. But we humans aren’t likely to go down without a fight.

3 Responses to “How scientists are fighting antibiotic resistance”

  1. Antibiotic Resistance Will Kill 300 Million People by 2050 – http://www.scientificamerican.com/article/antibiotic-resistance-will-kill-300-million-people-by-2050/
    Antibiotics: Unsafe At Any Level? – http://candidaplan.com/blog/379/antibiotics-unsafe-at-any-level/
    ANTIBIOTICS: More Harm Than Good – http://candidaplan.com/blog/1200/antibiotics-more-harm-than-good/
    ANTIBIOTICS MORE DANGEROUS THAN GMOs – http://candidaplan.com/blog/1306/antibiotics-more-dangerous-than-gmos/

  2. slcimmuno

    good article—thx for raising awareness. ABX resistance is scary, and folks are just starting to wake up to it. teixobactin was mentioned, and it has potential—but it’s years away from making it to market if it passes muster. one company advancing innovation on the ABX front is Cellceutix and its Host Defense Protein (HDP) Mimics platform (also sometimes referred to as defensin-mimetics). based on research originally done at U Penn (Polymedix), they have a class of compounds that mimic the immune systems response to fighting off bad bugs. its lead compound, Brilacidin, which performed comparably to Daptomycin (though as a single-dose not requiring 7 days of treatment) has been granted QIDP status by the FDA and soon will be entering Ph III for serious skin infections. brilacidin also showed efficacy against MRSA. other research is underway by Cellceutix targeting other gram-negative bacteria. anyway, it is good to see progress on the ABX front. hopefully more innovation is on the way and more incentives by government.

  3. exhibit44

    Large amounts of antibiotics in swine led to a terrible drug-resistant outbreak last year in the US. The animals had to be specially disposed of, to prevent horizontal transfer of the resistant genes.